Recombinant Human Cochlin Protein, CF

Cochlin, also known as Coch-5B2, is an N-glycosylated protein that constitutes the major protein component of inner ear extracellular matrix. Human Cochlin contains one LCCL/FCH and two VWF-A domains, all three of which may be deleted by alternate splicing (1 - 3). The predominant species in human, mouse, rat, and cow are the 63 kDa full length protein, two 40 and 46 kDa isoforms that lack the LCCL domain, and a 16 kDa isoform that lacks both VWF-A domains (3, 4). Cochlin is also susceptible to proteolysis between the LCCL and VWF-A1 domains (5). Mature full length human Cochlin shares 96% amino acid sequence identity with bovine, mouse, and rat Cochlin. Cochlin is secreted by inner ear fibrocytes and accumulates in acidophilic deposits of the cochlea and vestibule (6 - 10). Several point mutations in the LCCL domain are associated with the autosomal hearing loss disorder DFNA9, and the resulting mutant proteins exhibit altered aggregation and matrix association properties (2, 7, 11). The 63 and 16 kDa isoforms are also present in perilymph fluid (4). Cochlin is a target of IFN-gamma producing T cells in autoimmune sensorineural hearing loss (ASNHL) (12). Cochlin associates with the choline transporter CTL2 which itself is a target of autoimmune-mediated hearing loss (3, 13). Cochlin, absent in normal trabecular meshwork (TM) of the eye, is upregulated in glaucoma and is deposited around TM cells. It promotes the in vitro aggregation of TM cells and TM cell adhesion to collagen (14, 15). Polymorphisms within the second VFW-A domain are associated with glaucoma (15).